A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy

Miao, X.; Luo, Y.; Huang, X.; Lee, S. M. Y.; Yuan, Z.; Tang, Y.; Chen, L.; Wang, C.; Jiang, W.; Gao, W.; Song, X.; Yan, Y.; Pang, T.; Zou, Y.; Fu, W.; Wan, L.; Jramillo, J. G.; Knight, M.; Tan, T. K.; Rijal, P.; Townsend, A.; Sun, J.; Liu, X.; James, W. S.; Tsun, A.; Xu, Y.

doi:10.1101/2020.06.14.147868

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bioRxiv · 10.1101/2020.06.14.147868

A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy

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Abstract

In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provides a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain (NTD) of the viral S glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain (RBD) of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic virus infection in a standard assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.

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Miao, X., Luo, Y., Huang, X., Lee, S. M. Y., Yuan, Z., Tang, Y., Chen, L., Wang, C., Jiang, W., Gao, W., Song, X., Yan, Y., Pang, T., Zou, Y., Fu, W., Wan, L., Jramillo, J. G., Knight, M., Tan, T. K., Rijal, P., Townsend, A., Sun, J., Liu, X., James, W. S., Tsun, A., Xu, Y.. 2020-06-15. A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy. https://doi.org/10.1101/2020.06.14.147868

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